356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
1.
Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A, et al. Transplants of umbilicalcord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med
2004 Nov; 351(22):: 2276-2285.
2.
Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE, et al. Outcomes after
transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N
Engl J Med 2004 Nov; 351(22):: 2265-2275.
3.
Ballen KK, Gluckman E, Broxmeyer HE. Umbilical cord blood transplantation: the first 25 years
and beyond. Blood 2013 Jul 25; 122(4):: 491-498.
4.
Atsuta Y, Morishima Y, Suzuki R, Nagamura-Inoue T, Taniguchi S, Takahashi S, et al.
Comparison of unrelated cord blood transplantation and HLA-mismatched unrelated bone
marrow transplantation for adults with leukemia. Biol Blood Marrow Transplant 2012 May;
18(5):: 780-787.
5.
Eapen M, Rocha V, Sanz G, Scaradavou A, Zhang MJ, Arcese W, et al. Effect of graft source on
unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a
retrospective analysis. Lancet Oncol 2010 Jul; 11(7):: 653-660.
6.
Spellman SR, Eapen M, Logan BR, Mueller C, Rubinstein P, Setterholm MI, et al. A perspective
on the selection of unrelated donors and cord blood units for transplantation. Blood 2012 Jul 12;
120(2):: 259-265.
7.
Terakura S, Atsuta Y, Tsukada N, Kobayashi T, Tanaka M, Kanda J, et al. Comparison of
Outcomes of 8/8 and 7/8 Allele-Matched Unrelated Bone Marrow Transplantation and SingleUnit Cord Blood Transplantation in Adults with Acute Leukemia. Biol Blood Marrow Transplant
2016 Feb; 22(2):: 330-338.
8.
Ustun C, Giannotti F, Zhang MJ, Wang HL, Brunstein C, Labopin M, et al. Outcomes of UCB
transplantation are comparable in FLT3+ AML: results of CIBMTR, EUROCORD and EBMT
collaborative analysis. Leukemia 2017 Jun; 31(6):: 1408-1414.
9.
Barker JN, Krepski TP, DeFor TE, Davies SM, Wagner JE, Weisdorf DJ. Searching for unrelated
donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow.
Biol Blood Marrow Transplant 2002; 8(5):: 257-260.
10.
Kawashima N, Nishiwaki S, Shimizu N, Kamoshita S, Watakabe K, Yokohata E, et al. Outcomes
of strategic alternative donor selection or suspending donor search based on Japan Marrow Donor
Program coordination status. Int J Hematol 2018 May; 107(5):: 551-558.
11.
Terakura S, Nishida T, Sawa M, Kato T, Miyao K, Ozawa Y, et al. Prospective Phase 2 Study of
Umbilical Cord Blood Transplantation in Adult Acute Leukemia and Myelodysplastic Syndrome.
Biol Blood Marrow Transplant 2019 Sep 20.
12.
Sorror M, Maris M, Storb R, Baron F, Sandmaier B, Maloney D, et al. Hematopoietic cell
transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic
HCT. Blood 2005 Oct; 106(8):: 2912-2919.
13.
Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME, et al. Validation and refinement
of the Disease Risk Index for allogeneic stem cell transplantation. Blood 2014 Jun 5; 123(23)::
20
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
3664-3671.
14.
Bray RA, Hurley CK, Kamani NR, Woolfrey A, Muller C, Spellman S, et al. National marrow
donor program HLA matching guidelines for unrelated adult donor hematopoietic cell transplants.
Biol Blood Marrow Transplant 2008 Sep; 14(9 Suppl):: 45-53.
15.
Dehn J, Spellman S, Hurley CK, Shaw BE, Barker JN, Burns LJ, et al. Selection of unrelated
donors and cord blood units for hematopoietic cell transplantation: guidelines from the
NMDP/CIBMTR. Blood 2019; 134(12):: 924-934.
16.
Przepiorka D, Weisdorf D, Martin P, Klingemann H, Beatty P, Hows J, et al. 1994 Consensus
Conference on Acute GVHD Grading. Bone Marrow Transplant 1995 Jun; 15(6):: 825-828.
17.
Lee SJ, Vogelsang G, Flowers MED. Chronic graft-versus-host disease. Biology of Blood and
Marrow Transplantation 2003; 9(4):: 215-233.
18.
Kaplan E, Meier. P. Nonparametric estimation from incomplete observations. J Am Stat Assoc
1958; 53: 457-481.
19.
Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence
of competing risks: new representations of old estimators. Stat Med 1999 Mar 30; 18(6):: 695-706.
20.
21.
22.
Fine JP, Gray RJ. A Proportional Hazards Model for the Subdistribution of a Competing Risk.
Journal of the American Statistical Association 1999 1999/06/01; 94(446):: 496-509.
Cox DR. Regression Models and Life-Tables. Journal of the Royal Statistical Society Series B
(Methodological) 1972; 34(2):: 187-220.
Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics.
Bone Marrow Transplant 2013 Mar; 48(3):: 452-458.
23.
Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A, et al. Transplants of UmbilicalCord Blood or Bone Marrow from Unrelated Donors in Adults with Acute Leukemia. New
England Journal of Medicine 2004; 351(22):: 2276-2285.
24.
Elmariah H, Pratz KW. Role of Alternative Donor Allogeneic Transplants in the Therapy of Acute
Myeloid Leukemia. J Natl Compr Canc Netw 2017 Jul; 15(7):: 959-966.
25.
Frassoni F, Labopin M, Powles R, Mary JY, Arcese W, Bacigalupo A, et al. Effect of centre on
outcome of bone-marrow transplantation for acute myeloid leukaemia. Acute Leukaemia Working
Party of the European Group for Blood and Marrow Transplantation. Lancet 2000 Apr 22;
355(9213):: 1393-1398.
26.
Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, et al. T-cell-replete HLAhaploidentical hematopoietic transplantation for hematologic malignancies using posttransplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous
HLA-matched related and unrelated donor transplantation. J Clin Oncol 2013 Apr 1; 31(10)::
1310-1316.
27.
Shabbir-Moosajee M, Lombardi L, Ciurea SO. An overview of conditioning regimens for
haploidentical stem cell transplantation with post-transplantation cyclophosphamide. Am J
Hematol 2015 Jun; 90(6):: 541-548.
28.
Ruggeri A, Labopin M, Sanz G, Piemontese S, Arcese W, Bacigalupo A, et al. Comparison of
21
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation
in adults with acute leukemia. Leukemia 2015 Sep; 29(9):: 1891-1900.
29.
Tanaka M, Miyamura K, Terakura S, Imai K, Uchida N, Ago H, et al. Comparison of cord blood
transplantation with unrelated bone marrow transplantation in patients older than fifty years.
Biol Blood Marrow Transplant 2015 Mar; 21(3):: 517-525.
30.
Rio B, Chevret S, Vigouroux S, Chevallier P, Furst S, Sirvent A, et al. Decreased nonrelapse
mortality after unrelated cord blood transplantation for acute myeloid leukemia using reducedintensity conditioning: a prospective phase II multicenter trial. Biol Blood Marrow Transplant
2015 Mar; 21(3):: 445-453.
31.
Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, et al. Myeloablative Versus
Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and
Myelodysplastic Syndromes. J Clin Oncol 2017 Apr 10; 35(11):: 1154-1161.
32.
Terakura S, Kuwatsuka Y, Yamasaki S, Wake A, Kanda J, Inamoto Y, et al. GvHD prophylaxis
after single-unit reduced intensity conditioning cord blood transplantation in adults with acute
leukemia. Bone Marrow Transplant 2017 Sep; 52(9):: 1261-1267.
33.
Dahlberg A, Milano F. Cord blood transplantation: rewind to fast forward. Bone Marrow
Transplant 2017 Jun; 52(6):: 799-802.
34.
Barker JN, Kurtzberg J, Ballen K, Boo M, Brunstein C, Cutler C, et al. Optimal Practices in
Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies. Biol Blood Marrow
Transplant 2017 Jun; 23(6):: 882-896.
35.
Sharma P, Pollyea DA, Smith CA, Purev E, Kamdar M, Haverkos B, et al. Thiotepa-Based
Intensified Reduced-Intensity Conditioning Adult Double-Unit Cord Blood Hematopoietic Stem
Cell Transplantation Results in Decreased Relapse Rate and Improved Survival Compared with
Transplantation Following Standard Reduced-Intensity Conditioning: A Retrospective Cohort
Comparison. Biol Blood Marrow Transplant 2018 Aug; 24(8):: 1671-1677.
36.
Yamamoto H, Uchida N, Yuasa M, Kageyama K, Ota H, Kaji D, et al. A Novel Reduced-Toxicity
Myeloablative Conditioning Regimen Using Full-Dose Busulfan, Fludarabine, and Melphalan for
Single Cord Blood Transplantation Provides Durable Engraftment and Remission in
Nonremission Myeloid Malignancies. Biol Blood Marrow Transplant 2016 Oct; 22(10):: 1844-1850.
500
22
501
Figure legends
502
Figure 1. Treatment allocation according to CONSORT guidelines. AML, acute myeloid
503
leukemia; ALL, acute lymphoblastic leukemia; MDS, myelodysplastic syndrome; JMDP, Japan
504
Marrow Donor Program; UD, unrelated donor; CBT, cord blood transplantation; CR, complete
505
remission; BMT, bone marrow transplantation; PBSCT, peripheral blood stem cell transplantation;
506
SCT, stem cell transplantation.
507
508
Figure 2. Overall survival (OS) depicted with Kaplan–Meier estimates of cord blood
509
transplantation (CBT) and unrelated donor transplantation (UDT) recipients. There was no
510
statistically significant difference in OS between CBT and UDT (log-rank test, P = 0.59). HR,
511
hazard ratio.
512
513
Figure 3. Disease-free survival (DFS) depicted with Kaplan–Meier estimates of cord blood
514
transplantation (CBT) and unrelated donor transplantation (UDT) recipients. DFS was comparable
515
between CBT and UDT (log-rank test, P = 0.92). HR, hazard ratio.
516
517
Figure 4. Overall survival (OS) stratified by refined disease risk index (rDRI) in (A) cord blood
518
transplantation (CBT) and (B) unrelated donor transplantation (UDT). Int, intermediate.
519
520
Figure 5. Cumulative incidence of (A) non-relapse mortality (NRM) and (B) relapse after stem cell
521
transplantation according to graft source. The 2-year cumulative incidences of NRM were 14.7%
522
(95% CI, 8.9–21.7%) in CBT and 20.2% (95% CI, 12.6–29.1%) in UDT (Gray’s test, P = 0.38).
523
The 2-year cumulative incidences of relapse were 30.6% (95% CI, 22.4–39.2%) in CBT and 24.9%
524
(95% CI, 16.5–34.3%) in UDT (Gray’s test, P = 0.45).
23
7DEOH3DWLHQWDQGWUDQVSODQWFKDUDFWHULVWLFV
&%7
1R
1XPEHU
8'7
3 YDOXH
1R
3DWLHQWDJH\HDUVPHGLDQUDQJH
t
t
%RG\ZHLJKWNJPHGLDQUDQJH
t
t
6H[PDOH IHPDOH
'LDJQRVLV
$0/
$//
%$//
7$//
&5
&5
1RQ&5
0'6
$0/tGLVHDVHVWDWXVDWWUDQVSODQW
$//tGLVHDVHVWDWXVDWWUDQVSODQW
%$//
&5
&5
1RQ&5
&5
&5
1RQ&5
7$//
0'6tGLVHDVHVWDWXVDWWUDQVSODQW
&5DIWHUFKHPRWKHUDS\
(%
(%
2YHUWOHXNHPLD
'LVHDVHULVNLQGH[
/RZ
,QW
+LJK
9HU\KLJK
+&7&,
侔
1RRIDQWLJHQOHYHOPLVPDWFKHVLQ+/$$%'5
侔
1RRIDOOHOHOHYHOPLVPDWFKHVLQ+/$$%&'5
侔
'RVHLQWHQVLILHG̊
6WDQGDUGGRVH̋
'RVHUHGXFHG˒
0LVVLQJ
&RQGLWLRQLQJUHJLPHQ
*9+'SURSK\OD[LV
&\$SOXVV07;
7DFSOXVV07;
7DFSOXV00)
0LVVLQJ
71&&PHGLDQUDQJH
%0ʹ㻤NJ
t
3%6&ʹNJ
t &%ʹNJ
t
&'FHOOVPHGLDQUDQJH
t
%0ʹNJ
t
3%6&ʹNJ
&%ʹNJ
t
$0/DFXWHP\HORLGOHXNHPLD $//DFXWHO\PSKREODVWLFOHXNHPLD 0'6P\HORG\VSODVWLF
V\QGURPH (%H[FHVVEODVWV +&7&,KHPDWRSRLHWLFVWHPFHOOWUDQVSODQWVSHFLILFFRPRELGLW\
LQGH[
̊'RVHLQWHQVLILHGFRQGLWLRQLQJLQFOXGHGKLJKGRVHF\WUDELQHF\FORSKRVSKDPLGHWRWDOERG\LUUDGLDWLRQ7%, EXVXOIDQF\FORSKRVSKDPLGH7%,
̋6WDQGDUGGRVHFRQGLWLRQLQJLQFOXGHGEXVXOIDQF\FORSKRVSKDPLGH F\FORSKRVSKDPLGH7%, PHOSKDODQ7%,
˒'RVHUHGXFHGFRQGLWLRQLQJLQFOXGHGIOXGDUDELQHF\FORSKRVSKDPLGHZLWKRUZLWKRXW7%, IOXGDUDELQHPHOSKDODQ
&\$F\FORVSRULQH$ V07;VKRUWWHUPPHWKRWUH[DWH 7DFWDFUROLPXV 00)P\FRSKHQRODWHPRIHWLO
71&&WRWDOQXFOHDWHGFHOOFRXQWV %0ERQHPDUURZ 3%6&SHULSKHUDOEORRGVWHPFHOO &%FRUGEORRG
7DEOH0XOWLYDULDWHDQDO\VLVLQFOXGLQJERWK&%7DQG8'7
+5
ɻɻ150
&%7YV8'7
&,
3 YDOXH
1RVLJQLILFDQWYDULDEOH
ʷ
5HODSVH
ʷ
ɻɻɻɻU'5,
&%7YV8'7
ʷ
ɻɻɻɻ'LDJQRVLV
ʷ
ɻ')6
ʷ
ɻɻɻɻU'5,
&%7YV8'7
ʷ
'LDJQRVLV
ʷ
ɻɻ26
&%7YV8'7
ɻɻɻɻU'5,
ʷ
ʷ
'LDJQRVLV
ʷ
+5KD]DUGUDWLR &,FRQILGHQFHLQWHUYDO 150QRQUHODSVHPRUWDOLW\ &%7FRUG
EORRGWUDQVSODQWDWLRQ 8'7XQUHODWHGGRQRUWUDQVSODQWDWLRQ U'5,UHILQHG
'LVHDVH5LVN,QGH[ ')6GLVHDVHIUHHVXUYLYDO 26RYHUDOOVXUYLYDO
Figure 1
$! !" " (
' '
+801/,
!" " !" "!
" % ! "+84,
" " ! "" +81,
+ !#!!#! ,
+8//7,
" "0!"#&
+840,
*
" "0!"#&
+835,
* *
+806,
* +807,
#!!#! + *6)6
5)6 " ,+87/,
*
+865,
" # $
+8/0,
*
! "
& +83,
+85,
*
+82,
Figure 2
...
論文の公開元へ
